Morc1 knockout evokes a depression-like phenotype in mice
Morc1 knockout evokes a depression-like phenotype in mice
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DOI：
10.1016/j.bbr.2015.08.005
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发表时间：
2016-01-01
影响因子：
2.7
通讯作者：
Gass, P.
中科院分区：
文献类型：
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作者：
Schmidt, M.;Brandwein, C.;Gass, P.
Morc 1基因最近通过DNA甲基化和全基因组关联研究被确定为啮齿动物、灵长类动物和人类与早期生活压力相关的重度抑郁症的候选基因。到目前为止，还没有建立转基因动物模型来在行为水平上验证这些发现。在本研究中，我们研究了雌性C57 BL/6 N小鼠Morc 1功能缺失突变对情绪障碍行为相关性的影响，如强迫游泳测试，习得性无助范式，O型迷宫和暗光箱。我们可以证明，Morc 1（-/-）小鼠表现出增加的抑郁样行为，而没有行为异常的自发活动或焦虑样行为是可检测的。在Morc 1（-/-）小鼠和它们的野生型同窝小鼠之间，CORT血浆水平没有显著差异，然而令人惊讶的是，在Morc 1（-/-）动物中，海马中的总Bdnf mRNA水平上调。虽然进一步的工作将澄清，Morc 1（-/-）小鼠似乎是一个有前途的表观遗传学验证与早期生活压力相关的抑郁症的小鼠模型。(C)2015 Elsevier B. V.版权所有。
Morc1 gene has recently been identified by a DNA methylation and genome-wide association study as a candidate gene for major depressive disorder related to early life stress in rodents, primates and humans. So far, no transgenic animal model has been established to validate these findings on a behavioral level. In the present study, we examined the effects of a Morc1 loss of function mutation in female C57BL/6N mice on behavioral correlates of mood disorders like the Forced Swim Test, the Learned Helplessness Paradigm, O-Maze and Dark-Light-Box. We could show that Morc1(-/-) mice display increased depressive-like behavior whereas no behavioral abnormalities regarding locomotor activity or anxiety-like behavior were detectable. CORT plasma levels did not differ significantly between Morc1(-/-) mice and their wildtype littermates, yet - surprisingly - total Bdnf mRNA-levels in the hippocampus were up-regulated in Morc1(-/-) animals. Although further work would be clarifying, Morc1(-/-) mice seem to be a promising epigenetically validated mouse model for depression associated with early life stress. (C) 2015 Elsevier B.V. All rights reserved.